The intervertebral disc contains three major components: a nucleus pulposus (a fluid-like component comprising proteoglycans and collagen), an annulus fibrosis (a flexible, collagen-based ring surrounding the nucleus pulposus) and a pair of cartilaginous endplates which help enclose the nucleus pulposus within the annulus fibrosus. A normal, healthy nucleus pulposus acts much like a pressurized fluid by transferring and distributing compressive load to the annulus fibrosis, thereby causing a slight expansion of the annulus fibrosus. However, injury and/or degeneration of the intervertebral disc in the human spine can be caused by disc herniation, rupture of the annulus, prolapse of the nucleus pulposus, mechanical instability of the disc and/or dehydration of the disc, thereby leading to back pain. In addition, damage or degeneration of the annulus fibrosus in the form of a herniation, tear and/or crack reduces its ability to resist the tensile stresses conferred by the nucleus pulposus. Thus, the disc experiences excessive bulging that may result in spinal cord and/or nerve root impingement and subsequent back pain. Further, the nucleus pulposus can leak into the foramenal spaces, causing irritation of nerve roots and foramenal stenosis.
Treatments such as discectomy, laminectomy, laminotomy and/or spine fusion procedures represent state of the art surgical treatment for disc problems. Typically, the goal of these treatments is to relieve pressure on the neural elements by eliminating the material causing stenosis or irritation of the neural elements. However, discectomy when performed alone can result in significant loss of disc height and frequently provides only temporary pain relief. Laminectomy/laminotomy procedures also provide only temporary relief by opening up the spinal canal and decompressing the spinal cord, which is susceptible to restenosis due to scar tissue formation at the operative site. Spine fusion is considered by some to be a last resort, “most” invasive procedure that eliminates the flexibility of the motion segment and usually involves permanent hardware implantation. Furthermore, fusing spinal segments has been linked to adjacent level disc degeneration. All of these techniques have the disadvantage that they require surgical intervention to carry out the treatment.
Percutaneous microdiscectomy has been suggested as a minimally invasive discectomy procedure but still carries the disadvantage of causing disc height loss. Chemonucleolysis has been used clinically for decades and relieves pressure on a disc herniation by breaking down the nucleus pulposus. In essence, chemonucleolysis is a chemical discectomy. Because the goal of this treatment is to basically digest the nucleus, the consequent reduction in viscosity of the nucleus pulposus makes it more susceptible to leakage. In addition, this procedure appears to be associated with a 1%, incidence of anaphylaxis which has caused patient deaths. Furthermore, the procedure is known to also cause disc height loss.
Because of the drawbacks associated with the conventional procedures, newer procedures have been developed with an aim towards relieving back pain without requiring invasive surgery and without reducing disc height and providing a longer-lasting therapeutic effect.
Injecting curable or hardening materials into the disc following discectomy has been suggested in order to provide a filler material for the space left by removal of the nucleus and/or annular defect. U.S. Pat. No. 6,206,921 (“Guagliano”) discloses a method of first removing the nucleus pulposus and/or herniated portion of the annulus fibrosis, then injecting a heated, resilient, natural rubber material that hardens upon cooling. U.S. Pat. No. 6,187,048 (“Milner”) discloses an in situ polymerizable nucleus pulposus replacement material that may be enclosed by an impermeable container to prevent leakage. However, these materials may be susceptible to leakage out of the nucleus pulposus if no balloon or sheath has been formed around the material, particularly if the annulus fibrosis has not been adequately repaired. Furthermore, the implant may be subjected to repeated loads exceeding its strength over the lifetime it is expected to function in the patient. The potential consequence of failure is generation of foreign particulate, which has been linked to osteolysis and chronic foreign body reactions.
Other treatment options, which do not require discectomy or nucleotomy, have also been explored. U.S. Pat. No. 6,126,682 (“Sharkey”) discloses a method of treating annular fissures by delivering energy and/or materials to localized places near the inner wall of the annulus fibrosus, particulary at the posterior margins, using a functional element. Heating the disc has the potential to “weld” defects and/or shrink disc tissues. However, the mechanism of heating the disc to weld defects is not well understood and may cause secondary problems such as tissue necrosis and nerve root damage. Sharkey also discloses delivering dissolved collagen, adhesives, cements or hydrogels to seal fissures in the annulus fibrosus using the surgical instrument and functional element. However, this delivery is restricted to local points along the inner wall of the annulus fibrosus for treating annular fissures.
Sharkey does not disclose providing a crosslinking agent in an amount effective to cause the crosslinking of any native molecular proteins of the disc, nor does Sharkey disclose depositing a sealant material into the center of the nucleus pulposus portion of the disc.
PCT Publication No. WO 00/62832 (“Haldimann”) discloses an in situ curable sealant material that repairs defects in the disc annulus to prevent leakage of nucleus pulposus material. In some embodiments, Haldimann discloses that the sealant material is made of two precursor components: a buffered protein solution (including collagen) and a bifunctional crosslinking agent (including PEG with an activated terminal group). Typically, this injectable material adheres to the surrounding tissues by mechanical interlocking. In some embodiments, Haldiman discloses that covalent bonds are formed between the preferred hydrogel bio-compatible material and the surrounding annulus fibrosus tissue to further increase and secure the attachment of the sealant to the annulus fibrosus tissue in the proximity to the defect in the annulus fibrosus. There is also disclosed a method of adding “artificial nucleus pulposus material” to achieve a volume comparable to a normal nucleus pulposus followed by sealing the annulus.
Haldiman does not disclose providing the crosslinking agent in an amount effective to cause the crosslinking of any of the native molecular proteins of the disc. Haldiman does not disclose depositing the sealant material into the nucleus pulposus.
PCT Patent Publication No. WO 01/70151 (“Aksan”) discloses a method of strengthening and stabilizing collagenous tissues comprising the steps of heating to shrink the collagen followed by crosslinking with a non-toxic agent. The treatment is mainly focussed on glenohumeral instability and loose skin problems, but application of capsular shift procedures used to repair injuries of the spine is also mentioned. However, the crosslinking treatment always follows a thermal shrinkage step in the disclosed procedure. Thermal shrinkage is very difficult to achieve in the intervertebral disc beyond a local region without inducing damaging effects and is likely to cause a highly nonuniform tissue morphology. The crosslinking described is focused on collagen molecules, which exist in relatively small proportions in the nucleus pulposus of the spine (˜5%).
Aksan does not specifically disclose injecting the crosslinking agent into the intervertebral disc portion of the spine. Aksan does not disclose any method of crosslinking an untreated protein component of the disc.
U.S. Pat. No. 4,931,546 (“Tardy”) discloses a method for crosslinking collagen comprising exposing the collagen to a solution of periodic acid or a periodate, then allowing spontaneous crosslinking to occur from the aldehyde groups formed during exposure. Similarly, U.S. Pat. No. 5,972,385 (“Liu”) discloses a method of oxidizing polysaccharides, then reacting the oxidized product with collagen and adding a growth factor, and discloses application of material so formed in spinal fusion augmentation. Neither Tardy nor Liu describes in situ crosslinking of native living tissues, particularly in the spine or intervertebral disc.
Accordingly, there is a need for a minimally invasive method of treating pathological intervertebral discs that relieves back pain and encourages long-term disc stability and pain prevention by maintaining disc height, preventing nucleus leakage posteriorly, relieving pressure on a disc herniation, and inducing less alteration of the normal spine biomechanics.